title: Telmisartan reduces mortality and left ventricular hypertrophy with sympathoinhibition in rats with hypertension and heart failure.
abstract: BACKGROUND
  Angiotensin II type 1 receptor (AT1R) blockers have various benefits on hypertension and/or heart failure. We demonstrated that telmisartan (TLM), an AT1R blocker, causes sympathoinhibition by reduction of reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) of stroke-prone spontaneously hypertensive rats (SHRSPs). The aim of this study was to determine whether TLM improves survival in rats with hypertension and heart failure.
  
  
  METHODS
  Angiotensin II-infused and salt-loaded SHRSPs were divided into TLM-treated, candesartan cilexetil (CAN)-treated, and control groups. We determined the dose of TLM or CAN with similar depressor effects. We examined survival, urinary norepinephrine excretion (uNE) as a parameter of sympathoexcitation, ROS in the RVLM, and left ventricular (LV) end-diastolic pressure (LVEDP). LV hypertrophy (LVH) was assessed by echocardiography and heart/body weight.
  
  
  RESULTS
  Compared with the control group, TLM improved survival to a greater extent than CAN. At 4 weeks after treatment, ROS in the RVLM and uNE were significantly lower in the TLM-treated group than in the CAN-treated group, despite the similar depressor effects. At 8 weeks after the treatments, LVH and LVEDP were attenuated in the TLM-treated group compared with the CAN-treated group.
  
  
  CONCLUSIONS
  Our results suggest that TLM has the potential to reduce mortality, LVH, and LVEDP and that enhanced sympathoinhibition by reduction of ROS in the RVLM might be one of the mechanisms contributing to the beneficial actions of TLM in a model of rats with severe hypertension and heart failure.
authors.affiliation: Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy*; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D008526:Medulla Oblongata / Q000187:drug effects; D009638:Norepinephrine / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077333:Telmisartan; D013777:Tetrazoles / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D017382:Reactive Oxygen Species; D013777:Tetrazoles; C077793:candesartan cilexetil; D000077333:Telmisartan; D009638:Norepinephrine
keywords: ARB; blood pressure; brain; heart failure; hypertension; sy mpathetic nerve activity.